GUIDELINES ON UROLITHIASIS (Text updated May 2005) H.G. Tiselius (chairman), D. Ackermann, P. Alken, C. Buck, P. Conort, M. Gallucci, T. Knoll Eur Urol 2001;40:362-371 Introduction Urinary stone disease continues to occupy an important place in everyday urological practice. The average lifetime risk of stone formation has been reported in the range of 5-10%. A predominance of men over women (approx. 3:1) can be observed, with an incidence peak between the fourth and fifth decade of life. Recurrent stone formation is a common problem with all types of stones and therefore an important part of the medical care of patients with stone disease. Classification and Risk Factors Based on the chemical composition of the stone and the severity of the disease different categories of stone formers can be identified (Table 1). Irrespective of the previous course of the disease some patients need particular attention because of specific risk factors, summarized in Table 2. 182 Urolithiasis
Table 1: Categories of stone formers Description Abbreviation Non-calcium Infection INF stones Uric acid/sodium urate/ammonium urate UR Cystine CY Calcium First time stone former without residual stone stones or stone fragments S o First time stone former with residual stone or stone fragments S res Recurrent stone former with mild disease without residual stone(s) or stone fragments R m-o Recurrent stone former with mild disease with residual stone(s) or stone fragments R m-res Recurrent stone former with severe disease with or without residual stone(s) or fragments R s Stone forming patient with specific risk factor irrespective of otherwise defined category Risk Table 2: Specific risk factors for stone formation Start of disease early in life: < 25 years Stones containing brushite Only one functioning kidney Disease associated with stone formation Hyperparathyroidism Renal tubular acidosis (complete/partial) Jejunoileal bypass Crohn s disease Urolithiasis 183
Intestinal resection Malabsorptive conditions Sarcoidosis Hyperthyroidism Medication associated with stone formation Calcium supplements Vitamin D supplements Ascorbic acid in megadoses (>4 g/day) Sulphonamides a Triamterene a Indinavir a Anatomical abnormalities associated with stone formation Tubular ectasia (MSK) PUJ-obstruction Calix diverticulum/calix cyst Ureteral stricture Vesicoureteral reflux Horseshoe kidney Ureterocele PUJ = Pelvoureteral junction. a Non-calcium stones. Diagnostic Imaging Patients with renal stone colic usually present with characteristic loin pain, vomiting, and mild fever, and may have a history of stone disease. The clinical diagnosis should be supported by an appropriate imaging procedure. Imaging is imperative in patients with fever or a solitary kidney, or when the stone diagnosis is in doubt. 184 Urolithiasis
Routine examination involves a plain abdominal film of the kidneys, ureters and bladder (KUB) plus an ultrasound examination, an excretory pyelography (urography) or a spiral (helical) unenhanced computed tomography (CT). Excretory pyelography must not be carried out in patients: With an allergy to contrast media. With S-creatinine level > 200 µmol/l. Who take metformin. With myelomatosis. Special examinations that can be carried out include: Retrograde or antegrade pyelography. Scintigraphy. Laboratory Investigations Table 3: Analytical work-up in patients with uncomplicated stone disease Stone analysis Blood analysis Urinalysis In every patient Calcium Fasting morning one stone should Albumin a spot urine sample be analysed Creatinine Dip-stick test: Urate b ph Leucocytes/bacteria c Cystine test d a Either calcium + albumin or free calcium ion concentration. b Optional analysis. c Urine culture in case of bacteriuria. d Cystine test if cystinuria cannot be excluded by other means. Urolithiasis 185
Table 4: Analyses in patients with complicated stone disease Stones analysis In every patient one stone should be analysed Blood analysis Calcium Albumin a Creatinine Urate b Potassium Urinalysis Fasting morning spot urine sample Dip-stick test ph Leucocytes/bacteria Cystine test 24-hour urine collection c Calcium, oxalate, citrate, urate d, creatinine, volume, magnesium b,e, phosphate b,e,f, urea b,f, sodium b,f, chloride b,f, potassium b,f a Either calcium + albumin or free calcium ion concentration. b Optional analysis. c 24-hour urine can be replaced by collections during other periods of the day. d In samples that have not been acidified. e Magnesium and phosphate are necessary for calculations of estimates of the ion activity products of CaOx and CaP, respectively. f Urea, phosphate, sodium and potassium reflect dietary habits. 186 Urolithiasis
Table 5: Analytical programme for metabolic evaluation of patients with stone disease related to category Category Blood analysis Urinalysis Prevention follow-up INF S-creatinine Culture, ph Yes UR S-urate Urate, ph Yes S-creatinine CY S-creatinine Cystine, ph Yes S o Yes (see Table 3) Limited urinalysis No (see Table 3) S res Yes (see Table 4) Yes (see Table 4) Yes R m-o Yes (see Table 3) Limited urinalysis No (see Table 3) R m-res Yes (see Table 4) Yes (see Table 4) Yes R s Yes (see Table 4) Yes (see Table 4) Yes Risk Yes (see Table 4) Yes (see Table 4) Yes S = Serum. Treatment Pain Relief Pain relief can be achieved with the administration by various routes of the following agents: diclofenac sodium (Voltaren) indometacin ibuprofen hydromorphone hydrochloride + atropine sulphate (dilaudid-atropine) methamizol pentazocine and tramadol. Urolithiasis 187
Treatment should be started with an NSAID and changed to an alternative drug if the pain persists. Hydromorphone and other opiates without simultaneous administration of atropine should be avoided. Diclofenac sodium affects glomerular filtration rate in patients with reduced renal function, but not in patients with normal renal function. When spontaneous stone passage is anticipated 50 mg suppositories or tablets of diclofenac sodium administered twice daily during 3-10 days might be useful in reducing ureteral oedema and the risk of recurrent pain. Passage of stone and evaluation of renal function should be confirmed with appropriate methods. Retrieved stone(s) should be analysed. When pain relief cannot be achieved by medical means, drainage by stenting or percutaneous nephrostomy, or by stone removal should be carried out. General Recommendations for Stone Removal For all patients in whom stone removal is planned, screening for bacteriuria must be carried out. Dip-stick tests are sufficient in uncomplicated cases. In others a urine culture is necessary. When the test is positive for bacteriuria, or the urine culture shows bacterial growth, or when there is suspicion of an infection, treatment with antibiotics should be started before the stone-removing procedure. In cases with clinically significant infection and obstruction, several days of drainage procedures by a stent or a percutaneous nephrostomy should precede the active intervention for stone removal. Extracorporeal shock wave lithotripsy (ESWL), percutaneous 188 Urolithiasis
nephrolithotomy (PNL), ureteroscopy (URS) and open surgery are all contraindicated in patients with coagulation disorders. ESWL, PNL and URS are contraindicated in pregnant women. Indications for Active Stone Removal The size, site and shape of the stone influence the decision on how to deal with it. Spontaneous stone passage can be expected in up to 80% of patients with stones not larger than 4 mm. For stones with a diameter exceeding 7 mm the chance of spontaneous passage is low. The overall passage rate is 25% for proximal, 45% for mid, and 70% for distal ureteral stones. Stone removal is usually indicated for stones with a diameter exceeding 6-7 mm, and is strongly recommended in patients with: persistent pain despite adequate medication, persistent obstruction with impaired renal function, urinary tract infection, risk of pyonephrosis or urosepsis, bilateral obstruction and obstructing calculus in a solitary functioning kidney. Principles for Active Removal of Ureteral Stones For stones in different parts of the ureter and with different composition the most appropriate methods for stone removal are given in Table 6. Numbers 1, 2, 3 and 4 have been allocated to the procedures according to the consensus reached. The preferred alternative is always given the number 1, and when two procedures are considered equally useful they have been given the same number. Repeated sessions are frequently necessary for in situ ESWL treatment. Large and impacted stones have the highest retreat- Urolithiasis 189
Table 6: Principles for active removal of stones in the ureter Proximal ureter Radioopaque stones (1) ESWL in situ (2) ESWL after push-up (3) URS + disintegration (4) Perc. antegrade URS Infection stones, stones with infection Uric acid stones These stones should be managed like any other stones provided there is no obstruction and that a symptomatic infection has been adequately treated. (1) Stent + oral chemolysis (2) ESWL in situ + oral chemolysis (3) URS + disintegration (4) Perc. antegrade URS Cystine stones (1) ESWL in situ (2) ESWL after push-up (3) URS + disintegration (4) Perc. antegrade URS ESWL = includes piezolithotripsy; Perc. = percutaneous; UC = ureteral catheter; AB = antibiotics; PN = percutaneous nephrostomy catheter. ment rate. 190 Urolithiasis
Mid ureter Distal ureter (1) ESWL in situ, prone position a (1) ESWL in situ (1) URS + disintegration (1) URS + disintegration (2) UC /i.v. contrast + ESWL (2) UC + ESWL (2) Push-up + ESWL (3) Perc. antegrade URS (1) ESWL in situ, prone position a (1) ESWL in situ, i.v. contrast (1) URS + disintegration (1) URS + disintegration (2) UC /i.v. contrast + ESWL (2) UC + contrast + ESWL (2) Push-up + ESWL (3) PN + contrast + ESWL (2) Stent + oral chemolysis (3) Perc. antegrade URS (1) ESWL in situ, prone position a (1) ESWL in situ (1) URS + disintegration (2) URS + disintegration (2) UC /i.v. contrast + ESWL (2) UC + ESWL (2) Push-up + ESWL (3) Perc. antegrade URS a For lithotripters with the shock wave source below the patient. Videoendoscopic retroperitoneal surgery is a minimally invasive alternative to open surgery. Urolithiasis 191
Principles for Active Removal of Stones in the Kidney The success rate of ESWL is related to the concrement volume. Larger stones need more treatment sessions, but there is an ongoing debate as to whether large renal stones are best treated with ESWL or PNL. The recommended treatments according to stone size and composition are summarized in Table 7. Table 7: Principles for active removal of stones in the kidney Kidney stones < 20 mm Radioopaque stones (1) ESWL (2) PNL Infection stones, stones with infection (1) AB + ESWL (2) AB + PNL Uric acid stones (1) Oral chemolysis (2) Stent + ESWL + oral chemolysis Cystine stones (1) ESWL (2) PNL ESWL = includes piezolithotripsy; UC = ureteral catheter; AB = antibiotics. 192 Urolithiasis
Residual fragments, so-called clinically insignificant fragments, are common after ESWL treatment of stones in the kidney. For stones with a diameter exceeding 20 mm, double-j stenting before ESWL is recommended to avoid an accumulation of stones obstructing the ureter (steinstrasse). Kidney stones > 20 mm Complete or partial staghorn stones (1) PNL (1) PNL (2) ESWL (2) PNL + ESWL (3) PNL + ESWL (3) ESWL + PNL (4) Open surgery (1) AB + PNL (1) PNL (2) AB + ESWL with or (2) PNL + ESWL without stent (3) PNL/ESWL (3) AB + PNL + ESWL (4) ESWL + PNL (5) AB + ESWL + local chemolysis (1) Oral chemolysis (1) PNL (2) Stent + ESWL + oral (2) PNL + ESWL chemolysis (2) PNL/ESWL + oral chemolysis (3) ESWL + PNL (1) PNL (1) PNL (2) PNL + ESWL (2) PNL + ESWL (3)ESWL + PNL PNL = Percutaneous nephrolithotomy. Urolithiasis 193
For large ESWL-resistant stones, PNL with or without lithotripsy will be the best alternative for efficient removal. It should be observed that small stones residing in a calix might also cause considerable pain or discomfort. Preventive Treatment in Calcium Stone Disease The preventive treatment of patients with calcium stone disease should start with conservative measures. Pharmacological treatment should be instituted only when the conservative regimen fails. For a normal adult the 24-hour urine volume should exceed 2,000 ml, but the supersaturation level should be used as a guide to the necessary degree of urine dilution. Diet should be dictated by common sense, a mixed balanced diet with contributions from all nutrient groups, but avoiding any excesses. The further dietary recommendations should be based on the individual biochemical abnormalities. Pharmacological Treatment of Calcium Stone Disease The recommended forms of pharmacological treatment are summarized in Table 8. Pharmacological Treatment of Patients with Uric Acid Stones Prevention of uric acid stone formation can be accomplished with a high fluid intake producing a urine volume of at least 2,000 ml per 24 h. Alkalization is of fundamental importance thus, 3-7 mmol of 194 Urolithiasis
Table 8: Suggested selective treatment of calcium stone formers with known abnormalities in urine composition Treatment Treatment groups Thiazides 1 1) Hypercalciuria Thiazides + magnesium 1 2) Brushite stone formation Alkaline citrate 1) Hypocitraturia 1) RTA 2) Enteric hyperoxaluria 3) Low inhibitory activity 2 4) Other abnormalities Allopurinol 1) Hyperuricosuria Pyridoxine 1) Primary hyperoxaluria type 1 2) Mild hyperoxaluria Calcium supplements 1) Enteric hyperoxaluria Orthophosphate 3 1) Hypercalciuria 1 Potassium supplements are necessary to avoid hypokalaemia and hypocitraturia caused by hypokalaemic intracellular acidosis. 2 In case the inhibition of crystal growth or crystal aggregation has been assessed. 3 Orthophosphate is not a first-line alternative, but it can be used in patients with hypercalciuria who do not tolerate thiazides. Urolithiasis 195
potassium citrate or 9 mmol of sodium potassium citrate should be given 2-3 times daily. In cases of high levels of serum urate or urine-urate, a daily dose of 300 mg of allopurinol should also be given. To attain dissolution of uric acid stones, the high fluid regimen should be combined with 6-10 mmol of potassium citrate or 9-18 mmol of sodium potassium citrate three times daily and 300 mg of allopurinol also in cases of normal levels of serum and urine urate. Pharmacological Treatment of Patients with Cystine stones The fluid intake should give a 24-hour urine volume of more than 3,000 ml. To achieve this goal at least 150 ml has to be taken per hour. Alkalization should be undertaken so that the ph exceeds 7.5. This might be accomplished with potassium citrate 3-10 mmol in two to three divided doses. For patients with a 24-h cystine excretion above 3 mmol it is necessary to give tiopronin 250-2,000 mg/day or captopril (75-150 mg/day). Pharmacological Treatment of Stone Disease with Infection In those patients who have formed a stone composed of magnesium ammonium phosphate and carbonate apatite caused by urease-producing microorganisms, surgical stone clearance should be as complete as possible. Antibiotics should be given according to the resistance pattern and a long-term course is recommended to eradicate the infection. Summary Formation of concrements in the urinary tract is a pathological condition that afflicts people in most parts of the world 196 Urolithiasis
with a high prevalence. Urolithiasis thus puts a pronounced strain on the healthcare system. The recurrent nature of the disease makes it important not only to remove stones from the urinary tract and to assist in the spontaneous passage of stones, but also to offer these patients appropriate metabolic care. Less invasive treatment options have made the treatment of calculi relatively safe and routine. This short booklet text is based on the more comprehensive EAU guidelines (ISBN 90-70244-37-3), available to all members of the European Association of Urology at their website - http://www.uroweb.org. Urolithiasis 197